If setup correctly, not really. It looks and works the same.

As to the "if setup correctly" part, since flatpaks run in a sandbox/container, you have to tell it what access it has to the host system, for instance, for the chirp flatpak: 

   "finish-args": [
        "--share=ipc",
        "--share=network",
        "--socket=x11",
        "--socket=wayland",
        "--filesystem=home",
        "--device=all"

The ipc, x11, and wayland are needed for a GUI application (you can have command line flatpaks as well), the network is needed for downloading things ike Radio Reference, "home" gives the application access to the home directory and "device=all" is needed for access to serial ports. 

Thanks,

Richard